Hydrolytic kinetic resolution of cyclic substrates

• US 7,220,870 B2
• Filed: 01/05/2005
• Issued: 05/22/2007
• Est. Priority Date: 03/14/1995
• Status: Expired due to Fees

• Current Assignee: President and Fellows of Harvard College (Harvard Corporation)
• Original Assignee: President and Fellows of Harvard College (Harvard Corporation)
• Inventors: Jacobsen, Eric N., Tokunaga, Makoto, Larrow, Jay F.
• Primary Examiner(s): McKane; Joseph K.
• Assistant Examiner(s): Shiao; Rei-tsang
• Application Number:
  US11/029,887
• Publication Number:
  US 20050187392A1
• Time in Patent Office: 867 Days
• Field of Search: 549/90, 549/513, 548/954
• US Class Current: 549/90
• CPC Class Codes: C07B 53/00 Asymmetric syntheses
• CPC Class Codes: C07B 57/00 Separation of optically-active compounds
• CPC Class Codes: C07C 213/02 by reactions involving the formation of amino groups from compounds containing hydroxy groups or etherified or esterified hydroxy groups
• CPC Class Codes: C07C 247/14 with azido groups bound to carbon atoms of rings other than six-membered aromatic rings
• CPC Class Codes: C07C 2601/10 the ring being unsaturated
• CPC Class Codes: C07C 2601/14 The ring being saturated
• CPC Class Codes: C07C 2601/16 the ring being unsaturated
• CPC Class Codes: C07D 317/36 Alkylene carbonates; Substituted alkylene carbonates
• CPC Class Codes: C07F 7/083 Syntheses without formation of a Si-C bond
• CPC Class Codes: C07F 7/188 by reactions involving the formation of Si-O linkages
• CPC Class Codes: C07F 7/1892 by reactions not provided for in C07F7/1876 - C07F7/1888

Abstract

The present invention relates to a process for stereoselective or regioselective chemical synthesis which generally comprises reacting a nucleophile and a chiral or prochiral cyclic substrate in the presence of a non-racemic, chiral catalyst to produce a stereoisomerically- and/or regioisomerically-enriched product. The present invention also relates to hydrolytic kinetic resolutions of racemic and diastereomeric mixtures of epoxides.

Claims

1. A method of hydrolytic kinetic resolution represented by Scheme 1:

3. The method of claim 1 or 2, wherein R represents independently for each occurrence alkyl.

4. The method of claim 1 or 2, wherein R represents independently for each occurrence tert-butyl.

5. The method of claim 1 or 2 wherein R′

represents —

CH₂Cl, —

CH₂Br, —

CH₂OCH₂Ph, —

CH₂OSi(tert-butyl)(CH₃)₂ or —

CH₂OC(O)CH₂CH₂CH₃.

6. The method of claim 1 or 2, wherein the diol product has an enantiomeric excess greater than or equal to about 80%.

7. The method of claim 1 or 2, wherein the diol product has an enantiomeric excess greater than or equal to about 90%.

8. The method of claim 1 or 2, wherein the diol product has an enantiomeric excess greater than or equal to about 95%.

2. A method of hydrolytic kinetic resolution represented by Scheme 2:

9. A method of hydrolytic kinetic resolution represented by Scheme 3:

10. A method of hydrolytic kinetic resolution represented by Scheme 4:

11. The method of claim 9 or 10, wherein R represents independently for each occurrence alkyl.

12. The method of claim 9 or 10, wherein R represents independently for each occurrence tert-butyl.

13. The method of claim 9 or 10 wherein R′

represents —

CH₂Cl, —

CH₂Br, —

CH₂OCH₂Ph, —

CH₂OSi(tert-butyl)(CH₃)₂ or —

CH₂OC(O)CH₂CH₂CH₃.

14. The method of claim 9 or 10, wherein the terminal epoxide product has an enantiomeric excess greater than or equal to about 80%.

15. The method of claim 9 or 10, wherein the terminal epoxide product has an enantiomeric excess greater than or equal to about 90%.

16. The method of claim 9 or 10, wherein the terminal epoxide product has an enantiomeric excess greater than or equal to about 95%.